The newly founded unit Physics of Biological Function of biophysicist Thomas Gregor at Institut Pasteur is seeking to fill two open position at the engineer level to perform microscopy and imaging related research. Candidates with strong interest in interdisciplinary optical microscopy and biophysics research will be expected to build microscopes, run live imaging experiments and execute image processing and analysis routines.

Presentation of the unit and its research topics:

The Unit for the Physics of Biological Function at Institut Pasteur studies the basic physical principles that govern the existence of multicellular life. A core focus of the lab is to understand biological development–the complex process through which an organism grows from a single cell into a differentiated, multicellular organism–from a physics perspective. As such, we formulate and experimentally validate quantitative models that describe how individual cells interact and organize in order to generate complex life forms. Our main interests lie in:

  • multicellular pattern formation
  • transcriptional regulation in the context of development
  • molecular limits to biochemical sensing
  • emergence of collective behaviors in multicellular system
Description of a representative project:

The dynamic organization of the genome in time and space plays a crucial role in the functional specification of a cell. In particular the interplay between multiple distant enhancers and their target gene promoters has critical mechanistic consequences on gene activity patterns during cell differentiation and development. We are developing state-of-the- art high-resolution live imaging techniques to resolve multiple enhancers in space and time to correlate the 3D motion of the DNA polymer with gene activity. The challenge is to develop the right imaging modalities that optimize our need for high temporal and spatial resolution, and to image a large field of view with multiple (≥ 4) colors simultaneously.

Expected profile of the candidate:

Candidates will have a strong interest for collaborative and interdisciplinary research. They should have a proven successful track record equipped with a combination of the following skills:

  • live-cell microscopy, single molecule imaging
  • microscope design and implementation
  • hard- and software design for microscope control
  • computational image analysis

Ability to work independently and in collaboration with members of the lab and international collaborators in a dynamic, diverse and multinational group is essential. English is the working language.

Contact: thomas.gregor@pasteur.fr Applications should include a statement of research interests and motivation, a CV, and contact information for three references. Applications will be reviewed as soon as they are received. Funding is available for multiple positions; long-term funding is possible upon mutual agreement.

A PhD position is currently available at the Interdisciplinary Institute for Neuroscience (IINS) at Bordeaux to develop new super-resolution approaches for probing the fast and long-term dynamics of proteins in depth within complex tissues at high spatial resolution. This work will be based on a light-sheet microscope recently developed in the team and named soSPIM, which combines a single-objective with micro-fabricated chips featuring 45° mirrors1 . We already demonstrated the capabilities of this systems to perform multi-scale 3D imaging from the whole drosophila embryos scale down to the single cell scale. In addition, we have shown that the combination of the optical sectioning provided by the light sheet excitation with a high numerical objective enables to perform single molecule based super-resolution up to 30 µm deep above the coverslip. The aim of the project will be to improve the imaging capabilities of the soSPIM system to probe the various dynamics of adhesion proteins during the development of drosophila embryos at high spatial resolution. It will consist of implementing on the soSPIM system single particle tracking approaches and structured illumination microscopy methods2 to probe the fast and long-term dynamics of proteins respectively. To achieve this goal, we will implement both excitation beam shaping3 and adaptive optics4 in order to optimize the excitation and detection paths, respectively, and implement specific micro-fabrication processes to create devices dedicated to the imaging of drosophila embryos. In collaboration with G. Giannone team (IINS, Bordeaux) and N. Brown team (Gurdon Institute, Cambridge), we will then study the formation and maturation of adhesion sites during drosophila embryos development and their role in muscle tissue formation.

The  PICsL is located on the Luminy campus on two sites (IBDM and CIML ) that are within walking distance of each other. The PICSL offers a variety of state-of-the art imaging systems (multiphoton, confocal imaging, light sheet microscopy, super-resolution microscopy, electron microscopy). Mainly dedicated to developmental biology and immunology, the PICSL facility provides approaches for dynamic imaging, such as light sheet microscopy, super-resolution for tissue imaging (STED), multiphoton imaging but also more standard techniques such as time lapse imaging and confocal microscopy. Such methods are key to study quantitatively, the development of various animal species, and to decipher the operating mechanisms of the immune system, from molecules to whole organisms, such as Drosophila, C. elegans, Xenopus, chick, mice but also organotypic cultures and more recently organoids. The IBDM site also hosts an electron microscopy (EM) service. The EM service provides the scientific community with the expertise, material and electron microscopes necessary for molecular, cellular and tissue-level imaging by EM. Our service offer comprises the sample preparation with the following methods: negative staining, plastic embedding, immuno-labelling, high pressure freezing, freeze substitution, (cryo)-ultramicrotomy. We routinely use advanced imaging modes such as electron tomography (ET), Scanning Transmission Electron Microscopy (STEM), Scanning Electron Microscopy in « Serial Block-Face » mode, Correlative Light and Electron Microscopy (CLEM).

Microscopy systems available @PICsL

The BIC (Bordeaux Imaging Center) offers resources in photonic and electronic imaging, mainly in life, health and plant sciences. It is a core facility identified at the national level as IBISA that gathers 12 highly skilled engineers. It has the ISO9001 label. The different components of the BIC are: PHOTONIC imaging, ELECTRONIC imaging, PLANT imaging. The Bordeaux Imaging Center offers access to the most advanced bio-imaging techniques for fixed and live cell imaging such as video-microscopy, confocal microscopy, multiphoton microscopy, transmission electron microscopy and scanning electron microscopy. The BIC provides a unique set of high-end equipment for super- resolution microscopy such as STED confocal microscopy, FRAP video-microscopy, lifetime imaging FLIM for the measurement of molecular interactions. We also provide access to equipment for sample preparation such as ultra-microtoms, high pressure freeze (HPF) and we can host live samples.

Microscopy systems available @BIC